A5069306623- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Cancer Research and Treatments
- Glioma Diagnosis and Treatment
- RNA Interference and Gene Delivery
- Virus-based gene therapy research
- Immune Cell Function and Interaction
- Immune cells in cancer
- Cancer Immunotherapy and Biomarkers
- Nanoplatforms for cancer theranostics
- 3D Printing in Biomedical Research
- vaccines and immunoinformatics approaches
- Mesenchymal stem cell research
- Diet and metabolism studies
- MicroRNA in disease regulation
- Health and Medical Research Impacts
- Nanoparticle-Based Drug Delivery
- Neuroscience and Neuropharmacology Research
- Phagocytosis and Immune Regulation
- Adipose Tissue and Metabolism
- Chemokine receptors and signaling
- Monoclonal and Polyclonal Antibodies Research
- DNA Repair Mechanisms
- Elasticity and Material Modeling
- Neuroinflammation and Neurodegeneration Mechanisms
University of Florida
2016-2024
Allen Institute for Brain Science
2016-2020
Florida College
2018-2019
NIHR Southampton Biomedical Research Centre
2019
University of Southampton
2019
Pediatric Brain Tumor Foundation
2018
Abstract Chimeric antigen receptor (CAR) T-cell therapy targeting solid tumors has stagnated as a result of tumor heterogeneity, immunosuppressive microenvironments, and inadequate intratumoral T cell trafficking persistence. Early (≤3 days) presentation CAR cells post-treatment is superior predictor survival than peripheral Therefore, we have co-opted IL-8 release from to enhance through design for maximal antitumor activity in tumors. Here, demonstrate that receptor, CXCR1 or CXCR2,...
While mechanical properties of the brain have been investigated thoroughly, human tumors rarely directly quantified due to complexities acquiring tissue. Quantifying is a necessary prerequisite, though, identify appropriate materials for surgical tool testing and define target parameters cell biology tissue engineering applications. Since characterization methods vary widely soft biological synthetic materials, here, we developed method compatible with abnormally shaped tumors, mouse animal...
Anti-VEGF therapy prolongs recurrence-free survival in patients with glioblastoma but does not improve overall survival. To address this discrepancy, we investigated immunologic resistance mechanisms to anti-VEGF glioma models. A screening of immune-associated alterations tumors after treatment revealed a dose-dependent upregulation regulatory T-cell (Treg) signature genes. Enhanced numbers Tregs were observed spleens tumor-bearing mice and later treatment. Elimination CD25 blockade before...
Cancer vaccines initiate antitumor responses in a subset of patients, but the lack clinically meaningful biomarkers to predict treatment response limits their development. Here, we design multifunctional RNA-loaded magnetic liposomes potent immunity and function as an early biomarker response. These particles activate dendritic cells (DCs) more effectively than electroporation, leading superior inhibition tumor growth models. Inclusion iron oxide enhances DC transfection enables tracking...
Abstract Background Despite advancements in the successful use of immunotherapy treating a variety solid tumors, applications brain tumors have lagged considerably. This is due, at least part, to lack well-characterized antigens expressed within that can mediate tumor rejection; low mutational burden these limits abundance targetable neoantigens; and immunologically “cold” microenvironment hampers generation sustained productive immunologic responses. The field mRNA-based therapeutics has...
Immunotherapy has been demonstrably effective against multiple cancers, yet tumor escape is common. It remains unclear how brain tumors immunotherapy and to overcome this immune escape.
Purpose: Adoptive T-cell immunotherapy (ACT) has emerged as a viable therapeutic for peripheral and central nervous system (CNS) tumors. In cancers, optimal efficacy of ACT is reliant on dendritic cells (DCs) in the tumor microenvironment. However, CNS largely devoid resident migratory DCs to function antigen-presenting during immunotherapy. Herein, we demonstrate that cellular interactions between adoptively transferred tumor-reactive T bone marrow-derived hematopoietic stem progenitor...
In all cells, initiation of chromosome replication depends on the activity AAA+ initiator proteins that form complexes with origin DNA. bacteria, conserved, adenosine triphosphate (ATP)-regulated protein, DnaA, forms a complex origin, oriC, mediates DNA strand separation and recruitment machinery. Complex assembly activation requires DnaA-ATP, which differs from DnaA-ADP in its ability to cooperatively bind specific low affinity sites also oligomerize into helical filaments. The degree each...
With the presence of blood-brain barrier (BBB), successful immunotherapeutic drug delivery to CNS malignancies remains a challenge. Immunomodulatory agents, such as cytokines, can reprogram intratumoral microenvironment; however, systemic cytokine has limited access CNS. To bypass limitations systemically administered we investigated if RNA-modified T cells could deliver macromolecules directly brain tumors. The abilities cross BBB and mediate direct cytotoxic killing intracranial tumors...
The current standard of care treatments for medulloblastoma are insufficient as these do not take tumor heterogeneity into account. Newer, safer, patient-specific treatment approaches required to treat high-risk patients who cured by the therapies. Immunotherapy is a promising modality that could be key improving survival and avoiding morbidity. For an effective immune response, appropriate antigens must targeted. While with subgroup-specific genetic substitutions have been previously...
MD-PhD training programs train physician-scientists to pursue careers involving both clinical care and research, but decreasing numbers of stay engaged in research. We sought identify current research methods utilized by assess how effective they are promoting self-efficacy for research.The US students were surveyed April-May 2018. Students identified the participated in, was determined using a modified 12-item Clinical Research Appraisal Inventory.Responses received from 61 108...
The immunomodulatory effects of statins on vaccine response remain uncertain. Therefore, the objective this study was to determine if atorvastatin enhances pneumococcal-specific antibody titer following 23-valent pneumococcal polysaccharide vaccination.Double-blind, placebo-controlled, single-center randomized clinical trial entitled StatVax. Subjects were enrolled between June and July 2014 followed up through September 2014. 33 healthy volunteers signed informed consent after volunteer...
<p>Suppl Materials and Figures</p>
Abstract RNA vaccines have shown great promise as activators of immune responses against viral pathogens but their efficacy in cancer is unclear. Here, we describe a versatile, personalized mRNA-nanoparticle (RNA-NP) platform that can be customized to produce powerful anti-tumor activation, reprogram the brain tumor microenvironment, and predict vaccine just two days after treatment. Lipid mixtures (i.e. DOTAP, Cholesterol) with or without iron oxide nanoparticle-cores were complexed mRNA...
72 Background: Despite aggressive clinical interventions, glioblastoma (GBM) remains almost universally fatal. In a pilot, randomized, and blinded trial, we recently demonstrated that administration of RNA-loaded dendritic cell (DC) vaccines was associated with significantly improved progression-free overall survival in patients GBM (Mitchell et al, Nature 2015). Furthermore, outcomes correlated migration Indium-111-labeled DCs to vaccine-site draining lymph nodes (LNs) measured by SPECT/CT...
OBJECTIVES/SPECIFIC AIMS: The study aims to determine the current clinical research training interventions of MD-PhD programs and how effective they are in promoting self-efficacy. METHODS/STUDY POPULATION: A national survey trainees was conducted 2018 identify methods self-efficacy for skills. program directors coordinators from 108 institutions were asked distribute their students. Responses received 61 (56.5%). obtained 647 students all years training, representing 17.9% 3613 possible...
Study of T-cell traits that predict response to therapy is complicated by the challenge brain tumor antigens are largely uncharacterized. In other solid tumors, adoptive cell has been demonstrated be a highly efficacious immunotherapeutic strategy. Our OBJECTIVE demonstrate we have generated an platform leads expansion and persistence tumor-specific T lymphocytes without need for prior antigen identification. Instead, TCR Vβ expression can used both identify enrich population. We employ bone...
<p>FACS Antibodies</p>
<p>HSPC-derived DCs generated in vitro display DC phenotype and function.</p>